tbuckley/cabot-search huggingface dataset:
Assessment of long-term safety and efficacy of dupilumab in children with asthma (LIBERTY ASTHMA EXCURSION): an open-label extension study
Authors: Leonard B Bacharier, Jorge F Maspero, Constance H Katelaris, Alessandro G Fiocchi, Remi Gagnon, Ines de Mir, Theresa W Guilbert, Daniel J Jackson, Heribert W Staudinger, Elizabeth Laws, Leda P Mannent, Bolanle Akinlade, Jennifer Maloney, Kelsey Tawo, Faisal A Khokhar, Ning Li, Megan Hardin, Raolat M Abdulai, David J Lederer, Lacey B Robinson, Leonard B. Bacharier, Jorge F. Maspero, Constance H. Katelaris, Alessandro G. Fiocchi, Remi Gagnon, Ines De Mir, Theresa W. Guilbert, Daniel J. Jackson, Heribert W. Staudinger, Elizabeth Laws, Leda P. Mannent, Bolanle Akinlade, Jennifer Maloney, Kelsey Tawo, Faisal A. Khokhar, Ning Li, Megan Hardin, Raolat M. Abdulai, David J. Lederer, Lacey B. Robinson
Journal: The Lancet Respiratory Medicine (2023)
An engineered Escherichia coli Nissle strain prevents lethal liver injury in a mouse model of tyrosinemia type 1
Authors: Peng Gu, Li Xie, Tao Chen, Qin Yang, Xianglong Zhang, Ruofan Liu, Jiayin Guo, Rongjuan Wei, Dongping Li, Yong Jiang, Ye Chen, Wei Gong, Peng Chen
Journal: Journal of Hepatology (2023)
Validation of a new glucocorticoid-specific Patient-Reported Outcome Questionnaire (the Steroid PRO)
Authors: Susan Bridgewater, Mwidimi Ndosi, Jill Dawson, Pamela Richards, Christine Silverthorne, Emma Dures, Susan M. Goodman, Catherine Hill, Sarah L. Mackie, Joanna C. Robson
Journal: Annals of the Rheumatic Diseases (2023)

Objectives Glucocorticoids used in the treatment of inflammatory rheumatic conditions can impact on health-related quality of life. An underpinning qualitative study developed a long-list of candidate items for a treatment-specific patient-reported outcome (PRO) measure. The objective of this paper is to determine scale structure and psychometric properties of the Steroid PRO. Methods A cross-sectional survey of adults from the UK, USA, Australia and New Zealand, taking glucocorticoids for a rheumatic disease. Initial survey collected demographics, clinical information, 40 Steroid PRO candidate items and EuroQol-5 Dimensions- 5 levels (EQ-5D-5L). Follow-up, 3–5 days later, collected Steroid PRO candidate items and a condition-change (‘transition’) question. Analysis included Rasch measurement model, exploratory factor analysis (EFA), and hypothesis testing for discriminative validity, convergence validity and test–retest reliability. Results Total responses 946: UK n=743 (79%); USA n=139 (15%); Australia/New Zealand n=64 (7%); mean age 57.6 (SD=13.6); 833 (88%) women. Participants with inflammatory arthritis n=197 (21%), connective tissue disease and/or vasculitis n=402 (42%), giant cell arteritis and/or polymyalgia rheumatica n=347 (37%). Twenty-five items were removed due to lack of fit to Rasch model. Of the remaining items, EFA suggested four subscales: Social impact (4 items); Impact on appearance (3 items); Psychological impact (5 items); Treatment concerns (3 items). Rasch modelling supported a four-subscale structure and total score, confirming construct validity and reliability. Hypothesis testing confirmed discriminant and convergence validity. Intraclass correlation coefficient (total score) was 0.809 demonstrating excellent (test–retest) reliability. Conclusions The Steroid PRO is a 15-item, valid and reliable scale for measuring the impact of glucocorticoid therapy in people with rheumatic diseases.
When I use a word . . . Medicines regulation—the British Pharmacopoeia
Authors: Jeffrey K Aronson
Journal: BMJ (2023)

The 1858 Medical Act in the UK established what is now called the General Medical Council, and with it an order that the council should produce a <i>British Pharmacopoeia</i>, as a way of standardising the formulation of medicinal products. A follow-up Medical Act in 1862 made it clear that the intention was that the new pharmacopoeia would replace all three previous UK pharmacopoeias, the London, Edinburgh, and Dublin pharmacopoeias. The first edition of the <i>British Pharmacopoeia</i>, published in 1864, was full of errors and omitted many commonly used medicines, faults that were corrected in the 1867 edition. Since then many editions and supplementary volumes have appeared. Under section 4 of the 1968 Medicines Act a new British Pharmacopoeia Commission was established in 1970, to take over responsibility of production from the General Medical Council, and today a new edition of the <i>British Pharmacopoeia</i> appears every year.
Modulating the gut microbiota is involved in the effect of low-molecular-weight <i>Glycyrrhiza</i> polysaccharide on immune function
Authors: Wangdi Song, Yunyun Wang, Gongcheng Li, Shengnan Xue, Genlin Zhang, Yanyan Dang, Hebin Wang
Journal: Gut Microbes (2023)

Low molecular weight (6.5 kDa) Glycyrrhiza polysaccharide (GP) exhibits good immunomodulatory activity, however, the mechanism underlying GP-mediated regulation of immunity and gut microbiota remains unclear. In this study, we aimed to reveal the mechanisms underlying GP-mediated regulation of immunity and gut microbiota using cyclophosphamide (CTX)-induced immunosuppressed and intestinal mucosal injury models. GP reversed CTX-induced intestinal structural damage and increased the number of goblet cells, CD4+, CD8+ T lymphocytes, and mucin content, particularly by maintaining the balance of helper T lymphocyte 1/helper T lymphocyte 2 (Th1/Th2). Moreover, GP alleviated immunosuppression by down-regulating extracellular regulated protein kinases/p38/nuclear factor kappa-Bp50 pathways and increasing short-chain fatty acids level and secretion of cytokines, including interferon-γ, interleukin (IL)-4, IL-2, IL-10, IL-22, and transforming growth factor-β3 and immunoglobulin (Ig) M, IgG and secretory immunoglobulin A. GP treatment increased the total species and diversity of the gut microbiota. Microbiota analysis showed that GP promoted the proliferation of beneficial bacteria, including Muribaculaceae_unclassified, Alistipes, Lachnospiraceae_NK4A136_group, Ligilactobacillus, and Clostridia_vadinBB60_group, and reduced the abundance of Proteobacteria and CTX-derived bacteria (Clostridiales_unclassified, Candidatus_Arthromitus, Firmicutes_unclassified, and Clostridium). The studies of fecal microbiota transplantation and the pseudo-aseptic model conformed that the gut microbiota is crucial in GP-mediated immunity regulation. GP shows great potential as an immune enhancer and a natural medicine for treating intestinal inflammatory diseases.
Local and distant response to intratumoral immunotherapy assessed by immunoPET in mice
Authors: Louis Meyblum, Céline Chevaleyre, Sandrine Susini, Benoit Jego, Frederic Deschamps, Dimitri Kereselidze, Baptiste Bonnet, Aurelien Marabelle, Thierry de Baere, Vincent Lebon, Lambros Tselikas, Charles Truillet
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Despite the promising efficacy of immune checkpoint blockers (ICB), tumor resistance and immune-related adverse events hinder their success in cancer treatment. To address these challenges, intratumoral delivery of immunotherapies has emerged as a potential solution, aiming to mitigate side effects through reduced systemic exposure while increasing effectiveness by enhancing local bioavailability. However, a comprehensive understanding of the local and systemic distribution of ICBs following intratumoral administration, as well as their impact on distant tumors, remains crucial for optimizing their therapeutic potential. To comprehensively investigate the distribution patterns following the intratumoral and intravenous administration of radiolabeled anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and to assess its corresponding efficacy in both injected and non-injected tumors, we conducted an immunoPET imaging study. Methods CT26 and MC38 syngeneic colorectal tumor cells were implanted subcutaneously on both flanks of Balb/c and C57Bl/6 mice, respectively. Hamster anti-mouse CTLA-4 antibody (9H10) labeled with zirconium-89 ([ 89 Zr]9H10) was intratumorally or intravenously administered. Whole-body distribution of the antibody was monitored by immunoPET imaging (n=12 CT26 Balb/c mice, n=10 MC38 C57Bl/6 mice). Tumorous responses to injected doses (1–10 mg/kg) were correlated with specific uptake of [ 89 Zr]9H10 (n=24). Impacts on the tumor microenvironment were assessed by immunofluorescence and flow cytometry. Results Half of the dose was cleared into the blood 1 hour after intratumoral administration. Despite this, 7 days post-injection, 6–8% of the dose remained in the intratumoral-injected tumors. CT26 tumors with prolonged ICB exposure demonstrated complete responses. Seven days post-injection, the contralateral non-injected tumor uptake of the ICB was comparable to the one achieved through intravenous administration (7.5±1.7% ID.cm –3 and 7.6±2.1% ID.cm –3 , respectively) at the same dose in the CT26 model. This observation was confirmed in the MC38 model. Consistent intratumoral pharmacodynamic effects were observed in both intratumoral and intravenous treatment groups, as evidenced by a notable increase in CD8+T cells within the CT26 tumors following treatment. Conclusions ImmunoPET-derived pharmacokinetics supports intratumoral injection of ICBs to decrease systemic exposure while maintaining efficacy compared with intravenous. Intratumoral-ICBs lead to high local drug exposure while maintaining significant therapeutic exposure in non-injected tumors. This immunoPET approach is applicable for clinical practice to support evidence-based drug development.
Timed adoptive T cell transfer during chemotherapy in patients with recurrent platinum-sensitive epithelial ovarian cancer
Authors: Els M E Verdegaal, Saskia J Santegoets, Marij J P Welters, Linda de Bruin, Marten Visser, Caroline E van der Minne, Pita M de Kok, Nikki M Loof, Sanne Boekestijn, Inge Roozen, Inge M Westra, Pauline Meij, Sjoerd H Van der Burg, Judith R Kroep
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background The presence of T cells and suppressive myeloid cells in epithelial ovarian cancer (EOC) correlate with good and bad clinical outcome, respectively. This suggests that EOC may be sensitive to adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL), provided that immunosuppression by myeloid-derived suppressor cells and M2 macrophages is reduced. Platinum-based chemotherapy can alleviate such immunosuppression, potentially creating a window of opportunity for T cell-based immunotherapy. Methods We initiated a phase I/II trial ( NCT04072263 ) in patients with recurrent platinum-sensitive EOC receiving TIL during platinum-based chemotherapy. TILs were administered 2 weeks after the second, third and fourth chemotherapy course. Patients were treated in two cohorts with or without interferon-α (IFNa), as conditioning and TIL support regimen. The primary endpoint was to evaluate the feasibility and safety according to CTCAE V.4.03 criteria and the clinical response and immune modulatory effects of this treatment were evaluated as secondary endpoints. Results Sixteen patients were enrolled. TIL could be successfully expanded for all patients. TIL treatment during chemotherapy without IFNa (n=13) was safe but the combination with IFNa added to the chemotherapy-induced toxicity with 2 out of 3 patients developing thrombocytopenia as dose-limiting toxicity. Fourteen patients completed treatment with a full TIL cycle and were further evaluated for clinical and immunological response. Platinum-based chemotherapy resulted in reduction of circulating myeloid cell numbers and IL-6 plasma levels, confirming its immunosuppression-alleviating effect. Three complete (CR), nine partial responses and two stable diseases were recorded, resulting in an objective response rate of 86% (Response Evaluation Criteria In Solid Tumors V.1.1). Interestingly, progression free survival that exceeded the previous platinum-free interval was detected in two patients, including an exceptionally long and ongoing CR in one patient that coincided with sustained alleviation of immune suppression. Conclusion TIL therapy can be safely combined with platinum-based chemotherapy but not in combination with IFNa. The chemotherapy-mediated reduction in immunosuppression and the increase in platinum-free interval for two patients warrants further exploration of properly-timed TIL infusions during platinum-based chemotherapy, possibly further benefiting from IL-2 support, as a novel treatment option for EOC patients.
Geographic Variation in Qualified Health Plan Coverage and Prior Authorization Requirements for HIV Preexposure Prophylaxis
Authors: Kathleen A. McManus, Benjamin Fuller, Amy Killelea, Andrew Strumpf, Samuel D. Powers, Elizabeth T. Rogawski McQuade
Journal: JAMA Network Open (2023)

HIV preexposure prophylaxis (PrEP) is a key component of the Ending the HIV Epidemic (EHE) Initiative to curb new HIV diagnoses. In October 2019, emtricitabine/tenofovir alafenamide was added as an approved formulation for PrEP in addition to emtricitabine/tenofovir disoproxil fumarate; despite availability of another formulation with a similar prevention indication, variations in coverage may limit access.
Nosocomial SARS-CoV-2 Infections and Mortality During Unique COVID-19 Epidemic Waves
Authors: Nishi Dave, Daniel Sjöholm, Pontus Hedberg, Anders Ternhag, Fredrik Granath, Janneke D. M. Verberk, Anders F. Johansson, Suzanne D. van der Werff, Pontus Nauclér
Journal: JAMA Network Open (2023)

Quantifying the burden of nosocomial SARS-CoV-2 infections and associated mortality is necessary to assess the need for infection prevention and control measures.
Invoking a Medical Axiom for Buprenorphine Initiation—See One, Do One, Teach One
Authors: Scott G. Weiner
Journal: JAMA Network Open (2023)

Evangeline Gao, BA; Edward R. Melnick, MD, MHS; Hyung Paek, MD; Bidisha Nath, MBBS, MPH; R. Andrew Taylor, MD, MHS; Andrew J. Loza, MD, PhD
Self-Reported Neuropsychiatric Post–COVID-19 Condition and CSF Markers of Neuroinflammation
Authors: Shelli F. Farhadian, Hailey D. Reisert, Lindsay McAlpine, Jennifer Chiarella, Priya Kosana, Jennifer Yoon, Serena Spudich
Journal: JAMA Network Open (2023)

This case-control study assesses cerebrospinal fluid markers of neuroinflammation and blood-brain barrier disruption in individuals with post–COVID-19 condition who reported neuropsychiatric symptoms.
Perceived Interpersonal Racism and Incident Stroke Among US Black Women
Authors: Shanshan Sheehy, Hugo J. Aparicio, Julie R. Palmer, Yvette Cozier, Vasileios-Arsenios Lioutas, Julie G. Shulman, Lynn Rosenberg
Journal: JAMA Network Open (2023)

Importance Black individuals in the US experience stroke and stroke-related mortality at younger ages and more frequently than other racial groups. Studies examining the prospective association of interpersonal racism with stroke are lacking. Objective To examine the association of perceived interpersonal racism with incident stroke among US Black women. Design, Setting, and Participants The Black Women’s Health Study, a prospective cohort study of 59 000 Black women from across the US, assessed the longitudinal association between perceived interpersonal racism and stroke incidence. Stroke-free participants were followed up from 1997 until onset of stroke, death, loss to follow-up, or the end of the study period (December 31, 2019). Cox models were used to estimate hazard ratios (HRs) and 95% CIs, adjusting for major confounders, including education, neighborhood socioeconomic environment, and cardiometabolic factors. Data analysis was performed from March 2021 until December 2022. Exposure On a questionnaire completed in 1997, participants reported experiences of racism in everyday life and when dealing with situations that involved employment, housing, and interactions with police. Main Outcomes and Measures Strokes were identified through self-report on biennial questionnaires, medical records adjudication, and linkage with the National Death Index. Results In 1997, 48 375 Black women (mean [SD] age, 41 [10] years) provided information on perceived interpersonal racism and were free of cardiovascular disease and cancer. During the 22 years of follow-up, 1664 incident stroke cases were identified; among them, 550 were definite cases confirmed by neurologist review and/or National Death Index linkage. Multivariable HRs for reported experiences of racism in all 3 domains of employment, housing, and interactions with police vs no such experiences were 1.38 (95% CI, 1.14-1.67), a 38% increase, for all incident cases and 1.37 (95% CI, 1.00-1.88) for definite cases. For comparisons of women in the highest quartile of everyday interpersonal racism score vs women in the lowest quartile, multivariable HRs were 1.14 (95% CI, 0.97-1.35) for analyses that included all incident stroke and 1.09 (95% CI, 0.83-1.45) for analyses that included definite cases only. Conclusions and Relevance In this study, Black women who reported experiences of interpersonal racism in situations involving employment, housing, and interactions with police appeared to have an increased risk of stroke, even after accounting for demographic and vascular risk factors, suggesting that the high burden of racism experienced by Black US women may contribute to racial disparities in stroke incidence.
DOACs in Patients With Giant Coronary Artery Aneurysms After Kawasaki Disease
Authors: Kirsten B. Dummer, Koichi Miyata, Chisato Shimizu, Adriana H. Tremoulet, Jill Gleason, John B. Gordon, Jane C. Burns
Journal: JAMA Network Open (2023)

This case series examines outcomes among patients with giant coronary artery aneurysms after Kawasaki disease treated with direct oral anticoagulants (DOACs).
Adoption of Emergency Department–Initiated Buprenorphine for Patients With Opioid Use Disorder
Authors: Evangeline Gao, Edward R. Melnick, Hyung Paek, Bidisha Nath, R. Andrew Taylor, Andrew J. Loza
Journal: JAMA Network Open (2023)

Emergency department (ED) initiation of buprenorphine is safe and effective but underutilized in practice. Understanding the factors affecting adoption of this practice could inform more effective interventions.
Posttreatment Surveillance Imaging After Radiation for Head and Neck Cancer
Authors: Allen M. Chen, Jeremy P. Harris, Meng Gan, Rupali Nabar, Tjoson Tjoa, Yarah M. Haidar, Annie Truong, Daniel S. Chow, William B. Armstrong
Journal: JAMA Network Open (2023)

Importance The role of surveillance imaging after treatment for head and neck cancer is controversial and evidence to support decision-making is limited. Objective To determine the use of surveillance imaging in asymptomatic patients with head and neck cancer in remission after completion of chemoradiation. Design, Setting, and Participants This was a retrospective, comparative effectiveness research review of adult patients who had achieved a complete metabolic response to initial treatment for head and neck cancer as defined by having an unequivocally negative positron emission tomography (PET) scan using the PET response criteria in solid tumors (PERCIST) scale within the first 6 months of completing therapy. The medical records of 501 consecutive patients who completed definitive radiation therapy (with or without chemotherapy) for newly diagnosed squamous cell carcinoma of the head and neck between January 2014 and June 2022 were reviewed. Exposure Surveillance imaging was defined as the acquisition of a PET with computed tomography (CT), magnetic resonance imaging (MRI), or CT of the head and neck region in the absence of any clinically suspicious symptoms and/or examination findings. For remaining patients, subsequent surveillance after the achievement of a complete metabolic response to initial therapy was performed on an observational basis in the setting of routine follow-up using history-taking and physical examination, including endoscopy. This expectant approach led to imaging only in the presence of clinically suspicious symptoms and/or physical examination findings. Main Outcome and Measures Local-regional control, overall survival, and progression-free survival based on assignment to either the surveillance imaging or expectant management cohort. Results This study included 340 patients (mean [SD] age, 59 [10] years; 201 males [59%]; 88 Latino patients [26%]; 145 White patients [43%]) who achieved a complete metabolic response during this period. There was no difference in 3-year local-regional control, overall survival, progression-free survival, or freedom from distant metastasis between patients treated with surveillance imaging vs those treated expectantly. Conclusions and Relevance In this comparative effectiveness research, imaging-based surveillance failed to improve outcomes compared with expectant management for patients who were seemingly in remission after completion of primary radiation therapy for head and neck cancer.
Adverse Event Reporting in Randomized Clinical Trials for Multiple Myeloma
Authors: Mimi Najjar, John McCarron, Edward R. Scheffer Cliff, Katherine Berger, David P. Steensma, Samer Al Hadidi, Rajshekhar Chakraborty, Aaron Goodman, Eric Anto, Tom Greene, Douglas Sborov, Ghulam Rehman Mohyuddin
Journal: JAMA Network Open (2023)

Importance Cancer treatment can result in burdensome toxic effects that profoundly affect patient quality of life. In seeking to emphasize the efficacy of tested treatments, clinical trial reports may use subjective or minimizing terms to describe adverse events (AEs). Objective To evaluate patterns of AE reporting in multiple myeloma (MM) randomized clinical trials (RCTs) published between 2015 and early 2023. Design, Setting, and Participants For this cohort study, the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched to assess the prevalence of minimizing terms in MM RCTs published between January 1, 2015, and March 1, 2023. Minimizing terms were defined as subjective terms used to favorably describe the safety profile of the intervention. The terms searched included convenient , manageable , acceptable , expected , well-tolerated , tolerable , favorable , and safe . Final data analysis was performed on July 21, 2023. Main Outcomes and Measures The primary outcome was the occurrence of at least 1 minimizing term in an article. Univariate logistic regression analyses were performed to evaluate the association between the presence of at least 1 minimizing term and the actual incidence of grade 3 or 4 AEs, serious AEs, or grade 5 AEs. Results Of the 65 RCTs included, 56 (86%) used minimizing terms when describing treatment-emergent AEs. The most frequently used minimizing terms were well-tolerated or tolerable in 29 trials (45%), manageable in 18 (28%), and acceptable in 16 (25%). Grade 3 or 4 AE rate in the examined RCTs ranged from 23% to 94%, with a median of 75% (IQR, 59%-82%). A univariate regression analysis demonstrated no association between the use of minimizing terms and grade 3 or 4 AE rates (odds ratio [OR], 1.35 [95% CI, 0.88-2.10] per 10% AE rate increase; P = .17) or grade 5 AE rates (OR, 3.16 [95% CI, 0.27-12.7] per 10% AE rate increase; P = .45). Conclusions and Relevance These findings suggest that trial investigators and sponsors regularly use minimizing terms to describe toxic effects in MM trials, and use of this terminology may not reflect actual AE rates in these studies. Instead of using these terms, trial investigators should highlight event rates and patient-reported outcomes, to allow clinicians and patients to better evaluate the true tolerability of AEs.